Continuous Subcutaneous Insulin Infusion (CSII) of Insulin Aspart Versus Multiple Daily Injection of Insulin Aspart/Insulin Glargine in Type 1 Diabetic Patients Previously Treated With CSII

Hirsch, Irl B. MD
Bode, Bruce W. MD
Garg, Satish MD
Lane, Wendy S. MD
Sussman, Allen MD
Hu, Peter PHD
Santiago, Olga M. MD
Kolaczynski, Jerzy W. MD

¹University of Washington, Seattle, Washington
²Atlanta Diabetes Associates, Atlanta, Georgia
³Barbara Davis Center for Childhood Diabetes, Denver, Colorado
⁴Mountain Diabetes and Endocrine Center, Asheville, North Carolina
⁵Rainier Clinical Research Center, Renton, Washington
⁶Novo Nordisk Pharmaceuticals, Princeton, New Jersey
⁷University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey

Address correspondence and reprint requests to Irl B. Hirsch, MD, University of Washington Medical Center, 1959 NE Pacific St., Box 356176, Seattle, WA 98195. E-mail: [email protected]

Abbreviations: AUC, area under the curve; CGMS, continuous glucose monitoring system; CSII, continuous subcutaneous insulin infusion; MDI, multiple daily injection; SMBG, self-measured blood glucose

I.R.H. is a paid consultant for Aventis, Eli Lilly, Medtronic, and Novo Nordisk and has received grants from Novo Nordisk and Pfizer; B.W.B. is a paid consultant for Medtronic, Novo Nordisk, and Aventis and has received grants from Novo Nordisk, Aventis, and Medtronic; S.G. has received grants from Novo Nordisk; and W.L. has received honoraria from Aventis and Novo Nordisk.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

Received for publication 2 May 2004 and accepted in revised form 20 November 2004

Diabetes Care 28(3):p 533-538, March 2005.

OBJECTIVE

Multiple daily injection (MDI) therapy of bolus insulin aspart and basal insulin glargine was compared with continuous subcutaneous insulin infusion (CSII) with aspart in type 1 diabetic patients previously treated with CSII.

RESEARCH DESIGN AND METHODS

One hundred patients were enrolled in a randomized, multicenter, open-label, crossover study. After a 1-week run-in period with aspart by CSII, 50 subjects were randomly assigned to MDI therapy (aspart immediately before each meal and glargine at bedtime) and 50 subjects continued CSII. After 5 weeks of the first treatment, subjects crossed over to the alternate treatment for 5 weeks. During the last week of each treatment period, subjects wore a continuous glucose monitoring system for 48–72 h.

RESULTS

Mean serum fructosamine levels were significantly lower after CSII therapy than after MDI therapy (343 ± 47 vs. 355 ± 50 μmol/l, respectively; P = 0.0001). Continuous glucose monitoring profiles over a 24-h time period showed that glucose exposure was 24 and 40% lower for CSII than MDI as measured by area under the curve (AUC) glucose ≥80 mg/dl (1,270 ± 742 vs. 1,664 ± 1,039 mg · h · dl⁻¹; P < 0.001) and AUC glucose ≥140 mg/dl (464 ± 452 vs. 777 ± 746 mg · h · dl⁻¹, CSII vs. MDI, respectively; P < 0.001). Similar percentages of subjects reported hypoglycemic episodes (CSII: 92%, MDI: 94%) and nocturnal (12:00 A.M. to 8:00 A.M.) hypoglycemic episodes (CSII: 73%, MDI: 72%). Major hypoglycemia was infrequent (CSII: two episodes, MDI: five episodes).

CONCLUSIONS

In a trial of short duration, CSII therapy with insulin aspart resulted in lower glycemic exposure without increased risk of hypoglycemia, as compared with MDI with insulin aspart and glargine.